X-rays on Holmes' foot were negative, a league source told ESPNNewYork.com's Rich Cimini.
Holmes will have an MRI on Monday, according to a league source.
Holmes was carted away from the MetLife Stadium sideline and did not return to the game. He left the locker room on the back of a golf cart, his left foot booted and a pair of crutches by his side.
Jets coach Rex Ryan said after the game he did not having any specifics on the injury, which the team initially announced as a knee injury.
It's another tough break for the Jets. Pro Bowl cornerback Darrelle Revis tore his left ACL last weekend against the Miami Dolphins. In addition, rookie Stephen Hill and tight end Dustin Keller were inactive Sunday with hamstring injuries, and backup wideout Dedrick Epps went down early with a knee injury. Epps also will have an MRI on Monday.
"There's some great ability in that receiver room, so they'll have to pick up the slack," quarterback Mark Sanchez said.
Sanchez said he spoke to Holmes after the game as the receiver got treatment on the injury at the stadium. He said Holmes seemed in good spirits and addressed the play on which Holmes was injured -- a 4-yard catch and fumble that the 49ers returned for a touchdown.
"That's really too bad," Sanchez said. "You'd love him to hang on to the ball, but at the same time the guy's going down and hurt himself and kind of assumed the play was over so, another tough play."
The mood in the Jets' locker room was bleak as players processed a bad loss and the possibility of another major injury to a key player. The only light moment came when cornerback Kyle Wilson volunteered to play wide receiver a la Antonio Cromartie -- but players are aware of how Holmes' loss would affect the offense.
"It's not good. Santonio catches a lot of balls; the offense runs through him," receiver Chaz Schilens said, "so part of football is to pick it up and other guys have to make plays, including myself. So it is what it is."
Depending on the severity of Holmes' foot injury, the coaching staff probably won't have the luxury of that time as it prepares the team to meet the unbeaten Houston Texans on Oct. 8 in a Monday night game.
Information from ESPNNewYork.com's Rich Cimini was used in this report.